Aminergic control of early devlopment

早期发育的胺能控制

• 批准号: 180585-2006
• 负责人: Dubé, François
• 金额: $ 2.99万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=364814
• 关键词: Aminergic; control; early; devlopment

The functions of the neurotransmitter serotonin (5-HT, 5-hydroxytryptamine) are intensively studied and well known in the central nervous system and some other tissues.  The presence of 5-HT and its receptors in female reproductive tissues has been sporadically reported in vertebrate animals but it is in some invertebrates that precise functions of 5-HT in reproduction have been better described, in particular in molluscan species such as surf clam.  In this species, 5-HT triggers spawning in mature animals, and induces oocyte meiotic maturation when added to isolated oocytes, thus mimicking a process of activation normally set by the fertilizing sperm.  Using surf clam as a model, we have previously shown that their prophase I-arrested oocytes possess a 5-HT receptor whose activation triggers increased intracellular calcium and cAMP, and leads to full meiotic maturation.  Our specific objectives will be to further characterize a cloned putative clam oocyte 5-HT receptor by studying its signalling properties and pharmacological profile when transfected in mammalian host cells (HEK-293), and determine whether it is the specific receptor leading to meiotic maturation.   Other aminergic receptors expressed in clam oocytes will be investigated, including a cloned putative octopamine receptor, and tested for their capacity to influence meiotic maturation.  We will also verify to what extent observed cAMP rises elicited by 5-HT are causal in reinitiating meiosis in quiescent oocytes.  We will examine the capacity of specific activators and inhibitors of protein kinase A to alter meiosis reinitiation by 5-HT and establish possible links between internal cAMP levels and the MAPK signaling pathway relative to intracellular calcium rises.  Finally, the possible involvement of other biogenic amines such as octopamine and dopamine in the regulation of reproduction will be examined.  Our research program will clarify the mechanisms by which aminergic receptors are involved in reproductive and early developmental processes.  Our work will pave the way for understanding potential roles of a growing list of aminergic receptors of unknown local function but reported to be expressed in reproductive cells of not only invertebrate but vertebrate species, as well.

神经递质5-羟色胺(5-羟色胺，5-羟色胺)的功能在中枢神经系统和其他一些组织中得到了深入的研究和了解。脊椎动物雌性生殖组织中5-羟色胺及其受体的存在已有零星报道，但在一些无脊椎动物中，5-羟色胺在生殖过程中的确切功能得到了更好的描述，特别是在软体动物中，如文蛤。在该物种中，5-羟色胺在加入到分离的卵母细胞中时会触发产卵，并诱导卵母细胞减数分裂成熟，从而模拟受精精子正常设定的激活过程。我们先前已经证明，他们的前期I-停滞卵母细胞具有5-羟色胺受体，该受体的激活触发细胞内钙和cAMP的增加，并导致完全减数分裂成熟。我们的具体目标是通过研究克隆的推测的文蛤卵母细胞5-羟色胺受体在哺乳动物宿主细胞(HEK-293)中的信号特性和药理学特征来进一步表征它，并确定它是否是导致减数分裂成熟的特异性受体。此外，还将研究在文蛤卵母细胞中表达的其他胺能受体，包括克隆的推测的章鱼胺受体。并测试它们影响减数分裂成熟的能力。我们还将验证观察到的5-羟色胺引起的cAMP上升在多大程度上导致静止卵母细胞的减数分裂重新启动。我们将检测特定的蛋白激酶A激活剂和抑制剂改变5-羟色胺重新启动减数分裂的能力，并建立内部cAMP水平与与细胞内钙升高相关的MAPK信号通路之间的可能联系。我们将研究其他生物胺，如章鱼胺和多巴胺在生殖调节中的可能参与。我们的研究计划将阐明胺能受体参与生殖和早期发育过程的机制。我们的工作将为了解越来越多的胺能受体的潜在作用铺平道路，这些胺能受体具有未知的局部功能，但据报道不仅在无脊椎动物的生殖细胞中表达，而且在脊椎动物物种的生殖细胞中也表达。